In 1981 the project will focus on 3 general topics: 1 homeostatic fluctuations in ionized Ca2 ions, 2) the basis for the coronary arterial selectivity of calcium antagonists, and 3) alterations in calcium homeostasis in the human coronary artery and in models of atherosclerosis. Homeostatic fluctuations in Ca2 ions in acute dog models will continue to be examined, where preliminary data indicate rapid modulation of Ca2 ions may occur 1) by a change in serum citrate in settings where increased inotropic support is required, and 2) by changes in pH, where reduced Ca2 ions may protect against ventricular fibrillation. The basis for the coronary arterial selectivity (as compared to myocardial effects) of the calcium antagonist diltiazem appears to be due to differences in slow channel binding sites, an hypothesis that is being directly tested by low affinity binding techniques in cardiac and coronary arterial isolated membrane preparations. The calcium pools that mediate contraction in the human coronary artery are being examined in both normal and atherosclerotic tissue. Finally, the effect of a high cholesterol diet on the calcium pools in an animal model in the human coronary (rabbit aorta) is being examined.